Core D: Virus and Reservoirs ABSTRACT The mission of the Virus and Reservoirs Core (Core D) is to provide unparalleled molecular virology and sequencing support, services, facilities, consultation, and training to Penn CFAR investigators on campus, as well as the HIV/AIDS research community more broadly. Through this cutting-edge enabling technology combined with proactive scientific leadership, Core D seeks to advance AIDS research in high priority scientific directions. In the current reporting period, Core D has made substantial changes to both meet evolving needs, opportunities and priorities, and lead a forward-looking research agenda in the area of HIV cure, pathogenesis understanding of persistent viral reservoirs. These changes include new services as well as installation of a new leadership team comprised of Drs. Katharine Bar (Director) and Mohamed Abdel- Mohsen (Co-Director), and three senior HIV/AIDS scientists as Core Investigators (Drs. Frederic Bushman, Beatrice Hahn and George Shaw) to provide both specialized services and mentorship to the leadership team. To support its mission, the Virus and Reservoirs Core provides: (1) State-of-the-art molecular virology services including an extensive virus repository, viral assay services for economy of scale, an innovative cell product release assay for retroviral vector transduced ex vivo expanded cells to support innovative gene- and cell-therapy clinical trials, and quantitative real-time and digital droplet PCR platforms; (2) State-of-the-art sequencing services with analytical support, including Single Genome Amplification, amplicon sequencing by Illumina and Sanger platforms with custom processing and analytic support, and deep sequencing for complex populations or integration site analysis; (3) A new service based on novel transmitted/founder SHIV (SIV/HIV chimeric) viruses, to leverage the power of a new generation of SHIVs with tremendous opportunity for vaccine, pathogenesis and cure research; (4) Novel platforms for highly sensitive and specialized viral analysis including quantification of viral transcripts, proviral integration, single-copy viral load, single-cell analysis and related techniques; (5) Mentoring and education in appropriate application of these emerging technologies as well as training in implementation; and (6) Proactive outreach and leadership to promote research that exploits these technologies, including close collaboration with the HIV Reservoirs & Tissue Immunology SWG. In the current reporting period, Core D provided support to 119 investigators, generated over $5,000,000 in chargebacks, and supported more than 140 NIH-funded applications. Looking ahead to the upcoming cycle, in close collaboration with the Clinical, Immunology and Nonhuman Primate Cores and the Reservoirs and Tissue Immunology SWG, Core D will expand its services to galvanize basic and translational laboratory research, pre- clinical studies in nonhuman primates, and first-in-human clinical trials studying HIV reservoirs, virus persistence, and cure strategies.